Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Vyndamax: 61 mg
Pharmacology
Mechanism of Action
Tafamidis is a transthyretin (TTR) stabilizer that selectively binds to TTR at the thyroxine binding sites and stabilizes the tetramer of the TTR transport protein, slowing monomer dissociation into monomers which is the rate-limiting step in the amyloidogenic process. Tafamidis stabilizes both wild-type TTR tetramers and the tetramers of 14 TTR variants when tested clinically as well as 25 TTR variants tested ex vivo.
Pharmacokinetics/Pharmacodynamics
Distribution
Tafamidis: Vdss: 18.5 L
Metabolism
Tafamidis: Not fully established; glucuronidation has been observed
Excretion
Tafamidis meglumine: Feces: ~59% (unchanged); Urine: ~22% (glucuronide metabolite)
Tafamidis: Clearance: 0.236 L/hour
Time to Peak
Tafamidis: 4 hours
Half-Life Elimination
Tafamidis: ~49 hours
Protein Binding
Tafamidis: >99%, primarily TTR
Use in Specific Populations
Special Populations: Hepatic Function Impairment
In moderate hepatic impairment (Child-Pugh class B), tafamidis systemic exposure decreased (~40%) and clearance increased (~68%) compared to healthy subjects. Since TTR levels are lower with moderate hepatic impairment, exposure of tafamidis relative to the amount of TTR is sufficient to maintain stabilization of the TTR tetramer in these patients.
Use: Labeled Indications
Amyloid cardiomyopathy: Treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Dosage and Administration
Dosing: Adult
Amyloid cardiomyopathy: Oral:
Note: Tafamidis (Vyndamax) and tafamidis meglumine (Vyndaqel) are not substitutable on a per mg basis.
Tafamidis (Vyndamax): 61 mg once daily.
Tafamidis meglumine (Vyndaqel): 80 mg once daily.
Dosing: Geriatric
Refer to adult dosing.
Administration
Oral: Swallow capsules whole; do not crush or cut.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Adverse Reactions
There are no adverse reactions listed in the manufacturer's labeling.
Warnings/Precautions
Other warnings/precautions:
- Appropriate use: Equivalency: Tafamidis (Vyndamax) and tafamidis meglumine (Vyndaqel) are not substitutable on a per mg basis.
Pregnancy
Pregnancy Considerations
Information related to tafamidis use in pregnancy is limited and based on doses of 20 mg/day. Based on adverse events observed in animal reproduction studies, the manufacturer recommends pregnancy planning and pregnancy prevention in females of reproductive potential.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
